DIFFRACTION STUDIES OF THE BIOTIN VITAMERS

我们建议继续研究可能的反应物和 生物素介导的羧化反应产物。生物素是一种 维他命作为一种必需的辅因子 羧基酶和脱羧酶。我们的研究将集中在 围绕着目前正在进行的半反应机制的细节 建议吸收和转移生物二氧化碳 由这些酶催化。我们的主要工具将会很高 分辨率X射线衍射和量子化学技术，以及 这些将被用来研究电子学、振动学和 反应物和产物的几何性质以及 连接它们的最有可能的反应路径。我们的目标 是进一步完善这些技术，并将其应用于生物素 所有问题都没有解决。作为副产品，我们期待着新的方法 更强大、更简单、适用范围更广 应用于生物学有趣的问题。 生物素酶在新陈代谢中起着关键作用。丙酮酸 羧基酶催化糖异生的关键步骤。 乙酰辅酶A羧基酶在脂肪酸中起着这种作用 综合。其他依赖生物素的酶也与氨基有关。 酸和嘌呤代谢。证据的优势在于 所有的生物素酶都有一个共同的作用机制。这些酶 显示出惊人的遗传保护程度，超过了物种和 底物。因此，我们从学习中获得的知识是 适用于各种生化过程。我们的终极 目标是详细了解维生素的化学成分。

We propose to continue our studies of the likely reactants and products of biotin mediated carboxylation reactions. Biotin is a vitamin that serves as an obligatory cofactor for a host of carboxylase and decarboxylase enzymes. Our studies will center around the details of half reaction mechanisms currently being proposed for the uptake and transfer of biological carbon dioxide catalyzed by these enzymes. Our principal tools will be high resolution X-ray diffraction and quantum chemical techniques, and these will be employed to study the electronic, vibronic and geometrical properties of reactants and products as well as the most probable reaction pathways that interconnect them. Our goal is to perfect these techniques further and apply them to the biotin questions at large. As a by-product we expect the new approaches to be more robust, simpler to use, and suitable for wider application to biologically interesting problems. The biotin enzymes play pivotal roles in metabolism. Pyruvate carboxylase catalyzes the critical step in gluconeogenesis. Acetylcoenzyme A carboxylase plays that role in fatty acid synthesis. Other biotin dependent enzymes are involved in amino acid and purine metabolism. The preponderance of evidence is that all the biotin enzymes work with a common mechanism. These enzymes show a remarkable degree of genetic conservation, over species and substrates. Therefore, the knowledge we gain from our studies is applicable to a vide body of biochemical processes. Our ultimate goal is to understand the chemistry of the vitamin in detail.